The present invention generally relates to nutritional compositions. More specifically, the present invention relates to compositions for use in stimulating and improving wound healing.
Integuments surrounding tissues or organs of the body serve vital functions. One of the primary functions is to protect the soft internal tissues from physical trauma and bacteriological invasion. As a result, when an integument is lacerated or broken due to, for example, surgery or trauma, damage to the underlying tissues usually occurs.
For example, by virtue of its location at the body surface, the skin is constantly exposed to physical insult. Such insults range from minor abrasions to deep wounds that may penetrate to the subcutaneous tissues. The way in which the skin responds to this range of potential trauma varies depending on the severity of the trauma. In any case, however, a delay in the wound healing process increases the susceptibility to infection. Therefore, the acceleration of the healing process remains an elusive goal of the scientific community.
The pathophysiology of wound healing is complex and multifactorial. Current concepts suggest that healing involves the following mechanisms: (1) inflammation; (2) fibroblast proliferation, collagen synthesis; (3) angiogenesis; (4) wound contracture; and (5) epithelialization. See, for example, Roberts, Nutrition and Wound Healing, Nutrition in Critical Care, (Zaloga G. P. ed.) Mosby, St. Louis, pp. 525-544 (1994); and Cohen et al, Wound Healing-Biochemical and Clinical Aspects, (Lindblad W. J. eds.), W. B. Saunders, Philadelphia, pp. 1-630 (1992). Numerous factors, including metabolic factors, immune function, cytokines, eicosanoids, free radical production, and nutrient availability, affect these mechanisms.
Optimal wound healing requires delivery of a variety of nutrients to the wound. For example, nitrogen, vitamins (i.e. vitamin C) and minerals (i.e. zinc, magnesium, phosphorus, potassium) are required for wounds to heal. Id. Likewise, protein depletion impairs wound healing and, therefore, adequate protein intake is recognized to be essential for optimal wound healing. Still further, some studies suggest that supplementation of the diet with arginine improves wound healing in animals and humans. See, for example, Barbul et al, Intravenous Hyperalimentation with High Arginine Levels Improves Wound Healing and Immune Function, J. Surg. Res., 38:328-334 (1985); and Kirk et al, Arginine Stimulates Wound Healing and Immune Function in Elderly Human Beings, Surgery, 114:155-160 (1993).
In addition to the above nutrients, some researchers have postulated that carnosine may have an effect on wound healing when administered as a peptide via intradermal (ie. into the wound) or intraperitoneal injection. See, for example, Fitzpatrick et al, Carnosine, histidine and wound healing, Surgery, 91: 56-60 (1982); and Nagai et al, Action of carnosine and .beta.-alanine on wound healing, Surgery, 100: 815-820 (1986). Naturally, administering the peptide via intradermal and intraperitoneal injection is intrusive, and time-consuming.
In yet other studies dealing with ulcer prevention as opposed to healing, investigators have reported that N-acetyl-L-carnosine aluminum protects against the formation of gastric and duodenal ulcers in food deprived rats. See, for example, Okabe et al, Effects of N-Acetyl-L-Carnosine Aluminum (CL-1700) on Various Acute Gastric Lesions and Gastric Secretion in Rats, Japan J. Pharmacol, 31: 941-950 (1981); and Kunimi et al, Effects of CL-1700 on Duodenal Ulcer Formation in the Rat, Japan J. Pharmacol, 32: 1167-1170 (1982). As noted in these studies, some of the protective effect of this compound appears to result from the aluminum salt. The studies suggest that N-acetyl-L-carnosine aluminum and carnosine have different effects on ulcer formation.
Providing a suitable enteral diet or supplement that likewise stimulates wound healing would be advantageous. These diets can either be administered through a nasogastric tube or other external means or provided in liquid form that the patient drinks. Moreover, in many situations, it would be beneficial to support a trauma patient with a complete nutritional formula, while at the same time stimulate wound healing.
Numerous enteral formulations have been targeted for trauma and burn patients. These products include: Mead-Johnson's TraumaCal.RTM.; Sandoz's Impact.RTM.; Abbott Laboratories' Alitraq.RTM. and Perative.RTM.; and McGaw's Immun-Aid.RTM..
Although these products are used in an attempt to treat and/or provide nutritional requirements to such patients, the inventors of the present invention do not believe these products meet all the requirements of such patients. Delayed wound healing in such patients predisposes patients to infection, prolonged hospital stay, prolonged recovery and rehabilitation, increased hospitalization costs, and increased mortality.
Accordingly, a need exists for a new mode of therapy for improving wound healing in such patients.